In general, the invention relates to hemojuvelin fusion proteins and uses of such proteins.
Iron homeostasis is vitally important. Iron is required for many biological reactions and processes, including oxygen transport by hemoglobin, yet excessive iron can be toxic. To maintain proper serum levels, a complex system of iron transport and storage involving organisms employ iron storage protein ferritin, the iron transporter transferrin, and the transferrin receptor. When feedback controlling this system is disrupted, either insufficient iron (anemia) or iron overload (hemochromatosis) can result. Mutations in HFE2, the gene coding for hemojuvelin, have been previously been identified to cause iron overload in chromosome lq-linked juvenile hemochromatosis.
Hemojuvelin was identified as a member of the Repulsive Guidance Molecule (RGM) family of proteins, which include DRAGON and RGMa. The proteins were initially identified as being responsive to the transcription factor DRG11 (see, e.g., U.S. Patent Application Publication No. 2004/0014141, which is incorporated herein by reference) and their ability to promote neural adhesion and survival.